The dormant state is induced in mushroom spores of Agaricus bisporus by two metabolic inhibitors, both derived in the zygote by the action of tyrosinase upon the phenol, gamma-L-glutaminyl-4-hydroxybenzene (GHB). The major product of this reaction is a quinone whose strong sulfhydryl binding properties markedly curtail mitochondrial respiration and DNA polymerase alpha activity. This labile quinone is further oxidized to a second compound that impairs protein synthesis. The purified inhibitors markedly alter metabolism of neoplastic cells in vitro; however, the lability of these agents precludes in vivo application. Ongoing and proposed studies will carefully evaluate the potential of the precursor (GHB), its analogs, and related compounds, as specific therapeutic agents against human melanocarcinoma. The rationale of these studies rests upon the following unique characteristics of this natural system: 1) GBH is a stable phenol without mutigenicity or apparent toxicity for cells that lack tyrosinase, 2) the activation of GHB by hydroxylation and oxidation is dependent upon tyrosinase, 3) tyrosinase of human melanocarcinoma converts GHB to reactive metabolites, and 4) the reaction products of GBH interfere markedly with several key metabolic pathways. Antitumor properties of GHB and its analogs will be evaluated against human melanocarcinoma adapted to athymic mice.